Nuwiq

Uses

Nuwiq is an antihemorrhagic agent used for the treatment and prophylaxis of bleeding in patients of all ages with haemophilia A (congenital factor VIII deficiency).

Indicated for the treatment and prophylaxis of bleeding in patients of all ages with haemophilia A (congenital factor VIII deficiency) .

Nuwiq is also used to associated treatment for these conditions: Bleeding

How Nuwiq works

Haemophilia A is a sex-linked hereditary disorder of blood coagulation due to decreased levels of factor VIII:C. The disorder is associated with episodes of recurrent bleeding and profuse bleeding into joints, muscles or internal organs, either spontaneously or as results of accidental or surgical trauma .

Factor VIII circulates in the plasma as a hemostatically active protein complex that consists of factor VIII and a large carrier protein von Willebrand factor via a non-covalent binding interaction. This protein complex remains inactive until the coagulation cascade is activated which in turn activates factor VIII to be released from factor VIII/von Willebrand factor complex. Activated factor VIII acts as a cofactor for factor IX-mediated conversion of factor X to activated factor X. Activated factor X is critical in converting prothrombin into thrombin and sequentially, thrombin converts fibrinogen to fibrin for the formation of a blood clot .

Nuwiq is an antihemophilic factor that circulates as part of a protein complex with coagulant activity. As a replacement therapy, simoctocog alfa serves to restore the normal levels of factor VIII and allow effective blood clot formation in patients with haemophilia A.

Toxicity

Nuwiq is not expected to cause any adverse effects on the human reproductive functions or the human fetus. As genotoxicity studies and carcinogenicity studies are not applicable for recombinant products, such studies were not performed.

According to the single-dose toxicity study in rats, there were no deaths or notable life-threatening changes to the treatment and the highest non-lethal intravenous dose was determined to be < 10,000 IU/kg . In a repeated-dose toxicity study in monkeys, there was no evidence of systemic toxicity. There were no observable local reactions at the injection sites based on the findings of a rabbit local tolerance study .

Although the formation of neutralizing antibodies (inhibitors) to FVIII is a specified warning/precaution of simoctocog alfa treatment, there have been no cases of inhibitior development throughout clinical studies .

No cases of overdose have been reported with simoctocog alfa .

Food Interaction

Volume of Distribution

It is observed that simoctocog alfa is mainly distributed in the intravascular compartment.

At initial assessment following administration of 50 IU/kg simoctocog alfa in adolescent or adult patients with severe haemophilia A, the mean ± SD volume of distribution at steady state is 59.75 ± 19.76 mL/kg . The value in pediatric patients was 67.18 ± 13.27 mL/kg .

At 6-month assessment in adolescent or adult patients with the same dose, the value was 56.90 ± 9.07 mL/kg .

Elimination Route

At initial assessment following administration of 50 IU/kg simoctocog alfa in adolescent or adult patients with severe haemophilia A, the mean ± SD AUC (FVIII:C) was 17.95 ± 5.57 h·IU/mL/(IU/kg) . The mean ± SD maximum plasma concentration divided by the dose (Cmaxnorm) was 0.022 ± 0.003 IU/mL/(IU/kg) . The values of mean ± SD AUC (FVIII:C) and Cmaxnorm in pediatric patients were 10.92 ± 3.80 h·IU/mL/(IU/kg) and 0.017 ± 0.003 IU/mL/(IU/kg), respectively .

At 6-month assessment in adolescent or adult patients with the same dose, the mean ± SD AUC (FVIII:C) and Cmaxnorm were 16.86 ± 6.12 h·IU/mL/(IU/kg) and 0.021 ± 0.003 IU/mL/(IU/kg), respectively .

Half Life

At initial assessment following administration of 50 IU/kg simoctocog alfa in adolescent or adult patients with severe haemophilia A, the mean terminal half-life (T1/2) was 17.05 ± 11.23 h . The mean T1/2 in pediatric patients was 12.50 ± 4.17 h .

At 6-month assessment in adolescent or adult patients with the same dose, the value was 14.05 ± 4.70 h .

Clearance

At initial assessment following administration of 50 IU/kg simoctocog alfa in adolescent or adult patients with severe haemophilia A, the mean clearance rate (CL) was 2.96 ± 0.97 mL/h/kg . The mean CL in pediatric patients was 4.73 ± 1.87 mL/h/kg .

At 6-month assessment in adolescent or adult patients with the same dose, the value was 3.39 ± 1.42 mL/h/kg .

Elimination Route

In a non-bleeding state, simoctocog alfa is assumed to be cleared by low-density lipoprotein receptor-related protein (LRP) and low-density lipoprotein receptor (LDLR) as expected of endogenous factor VIII. In cases of bleeding or surgery, simoctocog alfa is believed to be consumed at the bleeding site as expected of factor VIII .

Innovators Monograph

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